In this S10 application, funding is requested for the purchase of a Xevo G2-XS mass spectrometer (Waters) equipped with an UPLC and an autosampler, shared among 14 NIH-supported and three NSF/DOE-supported users, with about 55 graduate students and postdocs from the labs of 7 Major Users, and 80 graduate students and postdocs from the labs of 10 Minor Users at GSU. NIH-supported users are expected to use more than 93% of the accessible user time. This need for a new workhorse instrument is precipitated by three key factors. First, the current workhorse instrument, Waters QTof Micro is outdated and old (15 years old) and is nearing its sustainable life. The Mass Spectrometry Facility also has an ABI-Sciex API 3200 LC-MS, which is also old (12 years) and is in a similar situation. Second, Waters has put the QTof Micro in the ?limited support? category with limited parts availability. We have recently had many problems that required service calls. The most notable was a motherboard problem in 2016. We were unable to get parts from Waters. We were very fortunate that a third- party service provider (Research Scientific Services, Gaithersberg, Maryland) was able to fix the problem with the Motherboard. However, this is not a sustainable solution. Third, Georgia State University has grown very quickly in the last decade in NIH-supported research. For example, the four units that participate in this application (Chemistry, Biology, Neuroscience, and Biomedical Science) brought in combined total of ~$13M in external funding in 2003 (the year we started working on purchasing the instrument to be replaced) and about $42M in 2018, mostly from the NIH. Further, GSU?s research portfolio increased from 43 NIH grants in 2009 (23 R01s) to 128 NIH grants (May 12, 2019 data) including 74 R01s, 15R21s, 13 U01s and U19s, 1 P01, and 1 P50. The lack of a modern mass spectrometer is becoming an urgent matter to be addressed, especially because of the realistic possibility for the existing instrument to breakdown, causing major disruption of NIH-funded research. The requested instrument will be incorporated into the existing Mass Spectrometry Facility, which has been in existing for 16 years with the PI of this application as the Director. There are routine and mature operational procedures in place already. GSU through its Chemistry Department provides very strong support to the Mass Spectrometry Facility with (1) a salary line for a Ph.D.-level Director (PI), (2) a salary line for support at the M.S.- level, (3) instrument service contract support, (4) space support, and (5) business/accounting support. Occasionally, a graduate assistant is provided when needed. The existing instruments have been on service contracts supported by the Department of Chemistry. All such support will continue. The requested Xevo G2-XS mass spectrometer is badly and urgently needed, and will allow us to meet the essential need and continue providing existing support with improved capability to NIH-supported projects. Furthermore, it will also allow us to provide expanded support in areas where sensitivity is critical including DNA, binding studies, nanoclusters, and protein/peptide modifications.